The overall goal of this proposal is to develop a hybrid, dual-modality x-ray computed tomography (XCT) and single photon emission computed tomography (SPECT) scanner for dedicated breast and axillary imaging, termed application specific emission and transmission tomography (ASETT). This noninvasive imaging tool is intended to provide volumetric, co-registered anatomical and functional imaging data for improved diagnosis of breast cancer. The XCT component of the system can provide structural three-dimensional images of the breast and axillary region with exposure near that of dual-view screening mammography, greatly improving the detectability of low contrast lesions in the breast, enhancing the spatially-dependent attenuation correction of the SPECT data, and facilitating better interpretation and quantification of the SPECT data by objectively guiding region of interest selection. This proposal represents the initial technology development for a dedicated breast ASETT system. A prototype, dedicated SPECT scanner has previously been investigated, and a gantry has been developed that facilitates a new class of hemispherical acquisition orbits about a pendant breast. This proposal will (1) extend the capabilities and performance characteristics of the SPECT camera and gantry, (2) develop and optimize the dedicated XCT scanner, and (3) integrate the two into a single system. The new SPECT system will have improved intrinsic spatial resolution (4.5mm) and intrinsic energy resolution (10% FWHM), and an expanded field-of-view, with fully computer controllable degrees of freedom. The XCT system will incorporate a novel x-ray source/filtration approach to mammographic imaging with a pseudo- monochromatic beam and a state-of-the-art, flat-panel, scintillator-based digital detector to reach <1mm isotropic reconstructed resolution. The ASETT detector system will be characterized and optimized for tomographic breast and axillary imaging. Novel orbits to sufficiently sample the pendant breast and axillary region will be developed, and trade-offs between sequential or simultaneous XCT/SPECT imaging, resolution, signal-to-noise, and radiation dose to the breast volume will be investigated. Appropriate phantoms will be used to quantitatively assess image quality and dose. Finally, the dual-modality ASETT system will be clinically evaluated with pilot patient studies.